The postmenopausal Estrogens/Progestins Intervention (PEPI-1) trial of 875 participants followed at seven centers for three years is the largest and longest randomized, double-blind, placebo-controlled clinical trial of hormone treatment in postmenopausal women--and the only long-term trial of estrogen-progestin regimens. It is the only long-term trial designed to compare the effects of estrogen replacement therapy (ERT) and combined (estrogen-progestin) hormone replacement therapy (HRT) on heart disease risk factors. It is also unique for the number of women who began ERT or HRT more than 10 years after the menopause. Details of the study design, hormone replacement regimens and study population are given in Project I, as are the major analyses of PEPI-1 data proposed for completion during the extended follow-up period. Project II, Studies of Repository Samples, was planned to utilize plasma, urine and other samples already collected, but not analyzed by the close of PEPI-1. Both Project I and Project II, submitted by the Coordinating Center to reflect the centralized activity necessary for a multicenter project, will be conducted with the Clinical Investigators as a cooperative project. Project III, submitted in parallel from each of the seven PEPI Clinical Centers, describes a three-year prospective observational follow-up study designed to: ensure PEPI women's safety and learn more about possible delayed adverse hormone effects; study treatment choices, compliance and reasons related to these decisions; and monitor long-term effects on heart disease risk factors and bone density. All participants will be invited to an annual clinic visit (conducted according to the established PEPI-1 protocol) that includes a medical history and limited examination, mammogram, endometrial biopsy, and standardized questions about quality of life, sexuality, symptomatology, and medication use. We will measure primary PEPI endpoints (HDL-cholesterol, blood pressure, insulin and fibrinogen) and their covariates, and bone density at the hip and spine.